Cyclic amino-acetals



Patented July 4, 1950 Richard Sallmann, Gelterkinden, and CharlesGraenacher, Riehen, Switzerland, assignors to. Ciba Limited, Basel,Switzerland av firm No Drawing. Application September 10. 1945', InSwitzerland October 4,

Serial No. 696,052. 1945 8 Claims. (CI. 260-338) According to thisinvention amino-compounds of acetal-like cyclieethers or amino-compoundsof the polyhydric alcoholsvcorresponding to. the said cyclic ethersaremade by treating an acetallike cyclic ether of a halogen-alcoholcontaining at leastZ hydroxylgroups at araised temperature with ammoniaor a primary or secondary amine, the reaction temperature being at least110 C. when a chlorinated acetal is used as starting material, and, if*d-esiredsplitting off the carbonylcompound bound inthe manner of anaoetal by treatment with an acid to form the salt of a polyoxy-amine.

The result obtained by this process is unexpected, because the chlorineatom in the acetallike cyclic ethers of polyhydric chlorinated alcohols.is. very strongly bound; thusit is known. that (vechloropropylenei-isopropy-1idene dioxide (acetone-glycerine a-chlorhydrin) when heatedfor 4 hours at 100 C. with potassium hydroxide re.-

mains unchanged. Therefore; it could not be foreseen that the presentprocess would lead to the desired result. 1

The acetal-like cyclic ethers used as starting materials may be derived,on the one hand, from pylene) -ethylidene dioxide, also namedacetaldehyde- ('y-chloropropylene) -acetal; ('y-chloropropylene)-benzylidene dioxide; also namedbenzaldehyde-e1ycerine-a-monochlorhydrin;; ('y-chloro-'f'ormaldehyde-a-monochlorhydriny ('y-chloropropropylene.)-isobutylidenedioxide; (fl chloropro- Dy1ene)-isQ-propylidene dioxide, also namedacetone-glycerinefi-ohlorhydrin; and, also propylene-chloropropylidenedioxide formed from trimethylene glycol andacrol'ein by additivecombination with hydrogen chloride. The acetal-like cyclic ethersserving as starting" materials, in so far-as they have not already beendescribed in the literature, can be made without d-ii liculty by methodsanalogous to those used for making" the known. compounds;

As primary amines there; may be: thoseof the aliphatic series, such asmethylamine, ethylamine, amylamine or dodecylamine, and also theproducts obtainable bythe reaction of ammonia with the halogen-acetalsto be used in the process. Among the secondary amines there may bementioned, those of the aliphatic series such as dimethylamine,diethylamine, di-amylamine or didodecylamine, and also those of theheterocyclic series such as piperidine.

The reaction temperature to be maintained during the reaction of thehalogen-compounds in accordance with the invention depends on thereactivity of the halogen atoms. Iodoand bromo-compounds react rat arelatively low temperature, whereas chloro-compounds require areaction'temperature exceeding C., forexample, -140 C. An excess ofammonia or of the primary or secondaryamine is generally of advantage.E'asilyvolatile reaction components, such as ammonia, dimethylamine orpiperidine, are advantageously caused to react inapresfiure vessel.Ammonia is advantageously caused to react in the absence. of a solvent.

The optional splitting off of the carbonyl com,- pound bound in themanner of anacetal, fromthe amino-acetals' obtained by the process maybe brought about by heating with a! strong acid, for example,hydrochloric. acid, in presence of water.

The cyclic amino-acetals obtainable from ammonia by the invention aregenerally mixtures of primary and. secondary amines. For example, thereare formed from cyclic acetalsof glycerinea-chlorhydrin by reactionwith. am onia, mixtures which consist. mainly of a product of the I 1 RIand. a product. of theformula In the above formulae, R1 and R2 eachrepresent hydrogen or a hydrocarbon residue.

From primary amines there are: generally orb:-

tained by the present process mixtures of secondary and tertiary amines.Tertiary amines obtainable according to the present invention may betransformed into quaternary ammonium compounds bytreating them with'alk'yla'ting or aralkylating agents, such as dialkyl sulfates,alkylhalides or aralkyl halides, for instance with di- .1

methyl sulfate, methyliodide or benzyl chloride.

The cyclic amino-acetals and also the 'corre sponding polyoxy-aminesderived therefromare generally liquids having a pronounced'basiccharacter, and can be used as intermediate products for making textileassistants, agents for combat- I ing pests or pharmaceuticalpreparations. They may be used, for example, for making amine soaps.Quaternary ammonium salts may be used as disinfecting agents.

Secondary amines of the invention may be designated as amines of thegeneral formula :wherein R is a member selected from the groupconsisting of alkyl radicals containing at least 2 ,-hydroxy. groups andalkyl radicals containing. at

least two hydroxy groups etherified with a car- -bonyl compound to'forma cyclic acetal, which amines have a pronounced basic character and, .inthe form of their hydrochlorides, are soluble in water. V I

The following examples illustrate the invention, the parts being byweight unless otherwise stated, and the relationship of parts by weightto parts by volume being the same as that of the 'ikilogram to thelitre:

Example 1 i I 200 parts of ('y-chloropropylene)-isopropy1idene dioxide(acetone-glycerine-a-chlorhydrin) are heated in a directly heated rotaryautoclave of VzA-steel with 300 parts of liquid ammonia for i 8 hours at130-140 C. A pressure of about 110 atmospheres develops. After blowingout the ex- "cess of ammonia, the reaction mass is dissolved in 300parts of water. Unchanged starting material can no longer be detected inthe aqueous solution. 120parts of solid caustic soda are added inportions, whereupon the mixture of bases separates in the form'of anoil.By fractional dis- "tillation' under reducedpressure the crude productcan 'be separated into two components. The

first boils at 65-66 C. under 14 mm. pressure and the second at 147-148"C. under 14 mm. pressure. They are both colorless liquids which aremiscible in all proportions'with organic solvents. Both amines dissolveeasily in cold water. only the lower boiling base is easily soluble inhot water. Their aqueous solutions have a strongly alkaline reaction.There are obtained under the conditions described above, as an averageof various tests, about one-third of the higher boiling base andtwo-thirds of the lower boiling base. This ratio can be varied to aconsiderable extent by changing the quantity of ammonia.

Investigation has shown that the lower boiling I I amine has the formulaH'2NYCHQ(IIHCHI and is to be designated as -aminopropylene)- However,

Exam le 2 A mixture of 30 -parts of ('y-chloropropyleneh jisopropylidenedioxide and 30 parts of diethylamine are heated in a pressure vessel for12 hours at -140 c. TheQreaction product is mixed with 40 parts ofconcentrated caustic soda solution, and the oil which rises tothesurface is separated. Since there is present in the oil a small quantityof unchanged starting material which can only be removed with difiicuity:by distillation, the baseis dissolved in a small quantity of water, andacidified .with sulfuric acid, while cooling thoroughly. vThewater-insoluble starting material can be extracted with ether. Thesolution, which iSllOW ciear, can be mixed with caustic soda in order'toseparate the base, and the latter is distilled after being dried withcaustic soda. It boils at 84-86 CQunde'r 14 mm. pressure. The base ofthe'formula is sparingly soluble inl wa ter and easily soluble inorganic solvents. r

f I" Ezrample 3 A solution of 30 parts of (y-chloropropylene)-'isopropylidene dioxide (acetone-glycerine-achlorhydrin) in 70' parts,by volume of an alcoholic solution'b'f dimethylamine of 25-per centstrength is heated for 15 hours at 130-140 0'. ,After removing thealcohol by distillation under reduced pressure at-40-50 C.,aconcentrated solution of caustic soda is added to the reaction product,and theoil; which separated is isolated. iAfterbeing dried with causticsoda, the product is distilled under reduced pressure. It boils at 163C.- under 12 mm..pressure. The fbase oi the formula I v NOHi-0HOH|' C IQ \O./. 1 0 CH has a strongly alkaline reaction, and is soluble'in wateras well as in organic'solvents.

Example 4 dried, it is distilled under reduced pressure. It

boils at ill-112 C. under 14.v mm. pressure. The base of the formula HE}HH N- om-oe -on,

H i t is sparingly soluble in water and easily soluble in all organicsolvents.

' Example '5 145 parts. of (y-chloropropylene) methylene dioxide(formal-glycerine-a-chlorhydrin) are heated in a rotary autoclave-ofVzA-steel with 250 parts of liquid ammonia for 8 hours at13 0-- 140 C.The reaction product is dissolved in 300 parts of water, and the base isthrown out of solution by the addition of120 parts of solid caustic sodawhile cooling. After being separated and dried with'solid caustic soda,the product is divided into two fractions by distillation under reducedpressure. The first fraction boils at 63*" C. under 12 mm. pressure and164 C.under'742 mm. pressure, and corresponds to the primary base. The(y-aminopropylene) -methylene dioxide so obtained is a colorless oil,which dissolvesin water and in organic solvents. Aqueous-solutionsthereof, when acidified WithHCLeVOIVfOlIIlflldehyde upon being heated. i

The second fraction boils-.at152-154 Cpunder 14 mm. pressure. .It is aviscous colorless oil, which is miscible in all proportions with waterand organic solvents. Its aqueous solutions have analkalinereaction.The-new aminehas the formula CHrH-H;

onkom-on;

ofi,

, Example 6 26.2 parts of ,formal-glycerin'eec-chlorhydrin are heatedwith 70 parts of an alcoholic solution of dimethylamine of 27.3 percent. strength in a pressure vessel for 15 hours at 130-140 C. At

the end of that period a test pflrtiom of the reaction =-.mixturei. iscompletely solubletimwater. The alcohol is removed from thereaction:mixture by distillation with the aid of a fractionating column,and then the residue, containing the hydrochloride of the base, isdissolved in a small quantity of water, and mixed with solid causticsoda while cooling until. the base separates in the form of an oil. Thelatter is isolated, and the last traces of residual base retained in thecaustic soda liquor are extracted with ether. After being dried withsolid caustic soda, the base is ld'ijs tilled.- The(-y-dimethyl-aminopropylene) -methylene-dioxide of the formulaN--oH=oH---oi1 on; v V H ofi, H

has a boiling point of 57 C. under12 mm. pressure -and' of 159-160" C.at atmospheric pressure,

and is a colorless oil soluble in all proportions in water and inorganic solvents.

. Example 7 26.2 parts of formal-glycerine-a-chlorhydrin and 30 parts ofdiethylamine' are heated in a pressure vessel for 12 hours at -140 C.The resulting base mixture, which is'intermingled with the hydrochlorideof the base, is stirred with 40 parts of concentrated caustic sodasolution, and the oil which separates is isolated. After being driedwith solid caustic soda the oil is distilled, advantageously with theaid of a fractionatingcolumn. A small quantity of a mixture of the newbase with unchanged starting material passes over initially, and thenthe pure base, (7 diethylaminopropylene) methylene dioxide, distils at.79-80 C. under 12 mm. pressure. The

water in organic solvents.

base isa colorless oil, which is easily soluble in Example 8 24.5 partsof formal-glycerine-a-chlorhydrin are heated in a pressure vessel with34 parts of piperidine for 12 hours at 130-140 C. The reaction productis worked up in the manner described in Example 6. The resulting(piperidine NY- propyiene) -methylene dioxide of the formula i H H H H HI 1/ CHi -EIii-" illie H rt H\H is a colorless base, which boils at109-111 C. under 12 mm. pressure, has an odour-faintly; resembling thatof piperidine, and dissolves easily in water and in organic solvents.

Example 9 separates, isis'olated; dried with caustic sodaandfractionatedwith the aid of afractionating col 'At 62-6310, under-14mm; pressure (7-? 2, era-.141

.aminopropylene) -ethylidine dioxideof the for.-

mula .i.

HFcHPcH-'oHr 11 on, distils in the form of a colorless oil ha vingaweakly basic odour, which boils at 164-165" C. under atmosphericpressure, and whichdissolves easily in water and in organic solvents.Its aqueous solutions have a strongly alkaline reaction and, afteracidification with a strong acid, liberate acetaldehyde when heated.

In fractionating the mixture of bases obtained v as described above asecond base passes over at 145-147 C. under l l mm. pressure. This baseis also easily soluble in water and in organic s01- -vents, andcorresponds to imino-di- ('y-propyleneethylidene dioxide) of thefollowing formula:

. 0 \O OHr- H.-(!3Hg cH-oH-'-orh 11 Core Example 10 2'7 parts of(y-chloropropylene) -ethylidene dioxide are heated in a pressure .vesselwith 34 parts of piperidine for 12 hours at 130-'-140 C. The reactionproduct is worked up in the manner described in Example 6.'y-piperidino-propyleneethylidene dioxide is obtained inthe form of acolorless baseQwhich distils at 106107"C. under 14-. mm. pressure. It issparingly soluble in cold Water and easily soluble in organic solvents.

Example 11 -32.8 parts of ('y-chloropropylene)- isobutylidene dioxide(prepared from glycerine-a-chlorhydrin and methylethyl ketone) areheated in a pressure vessel with 34 parts of pip'eridine for 12 hours at130-140 C., and the reaction product is worked up as described in.Example 6. The q-piperidino-propylene-isobutylidene dioxide so obtainedof the formula has a boiling point of 128 C. under 12 mm. pressure andis a colorless base, which is sparingly soluble in 'cold water andeasily soluble in organic solvents. Aqueous solutions of the base'becometurbid upon heating. Methyl-ethyl-keton'e is split off when the cyclicacetal is heated with hydrochloric acid. 1

Example 12 g 30 parts of ('y-aminopropylene) -isopropylidene dioxide areheated with part of 'y-chloropropylene isopropylidene dioxide for 12hours at 130-140,. ..C. with the exclusion. of; air.

The 1111 -19.8 -parts of 'y-chloro'propylene-benzy1idenedioxide'(prepared =fro'mglycerine-a-chlorhydrin and-benzaldehyd) are heated witha solution of 30 percent. strength of dimethylamine in methylalcohol-for- 12 hours'at 130-140 C. The methyl alcohol is then removedby distillation, and 'ydimethylamino-propylene-benzylidene dioxide ofthe formula can be recovered from the residue by a usual method in theform of a yellowish oily base, which boils at 91-1029 C1 under 0.01 mm.pressure. The product'issparingly soluble in water, but easily solublein'dilute aquebusacids, which latter cause rapid splitting upon heatingwith the separation of benzaldehyde.

xample 14 30 "parts 'of "acetone glycerine-a-chlorhydrin are heatedinapressure vessel with 68 part of an alcoholic solution of ammonia of 10per cent. strength and 4.3-parts of sodium carbonate of 12 hours'at'1'30-140 CI The alcohol is removed from the reaction solution bydistillation, and then E'the residueyis'worked as described in Example1= to recover the base- 1 In this manner a mixtureof primary andsecondary bases is obtained, which mixture,"whensubjected to fractionaldistillation, yields :the same products as those obtained in Example}.

a 27.5 parts "of (ychloropropylene) -ethylidene dioxide areheatedwith 30parts of diethylamine in a pressure vessel for 15 hours at ISO- C.

5 The partially crystalline reaction product is mixed first with4Q'parts of water and then with caustic soda until the base hascompletely separated in the formbfanbil; After isolating the product anddrying it with caustic soda, it is dis- 05 tilled under reducedpressure. At first a small quantity of unchanged starting materialpasses over, and then the base of the formula 16 distils 'at 87-89 0.under 14 pressure. It is a liquid having a weakly basic-odour, and issparingly soluble in water and easily soluble in organic solvents.

Example 16 30 parts of -aminopropylene)eisopropylidene dioxide aredissolved in 100 parts of distilled water. After theaddition-of 20 partsby volume of hydrochloric acid of 37 per cent. strength, the clearsolution is heated for one hour on the water bath. Acetone is evolved,and initially colorless solution becomes slightl red-brown. The excessof acid is then neutralized with sodium carbonate, and the hydrochlorideof y-aminopropylene glycol is decomposed by the addition of 9.5 parts ofcaustic soda. After being dried by evaporation under reduced pressure,the liberated amine is isolated by extraction with absolute alcohol, andthe alcohol is removed by distillation. The residue, which is a thicklyfluid oil, may be distilled under reduced pressure,3-aminopropanediol-(1z2) passes over at 152 C. under 12 mm. pressure.

Example 17 50 parts of the base of the formula CH; on,

\(v on; CH:

are dissolved in-200 parts by volume of sulfuric acid of per cent.strength. The solution is gradually heated to the boil in the course ofminutes whereupon the originally strong acetone odour disappears. Afterthe addition of barium carbonate until there is no' 'more acid reactionthere follows filtration. The filtrate is evaporated under reducedpressure; the base is obtained in the form of a. thick, brownishcolored'oil which solidifies into a soft amorphous mass. The base iseasily soluble in water or alcohol, but insoluble in ether. Its aqueoussolution shows a strongly alkaline reaction.

Example 18 2.0 parts of the base of the formula OH: 0 o GHQ-rH-&Hg

are mixed with 1.6 parts of-methy1icdideand al new quaternary. salt isan .unctuous, yellowish,

i mass which dissolves inwater to give aclear solution.

' Example 19 g 3.6 parts of the base of the formula are mixed with 1.4parts of dimethyl sulfate. After the mixtue'has beenallowed to stanolforone hour at room temperature it is heated on the steam bath for 10minutes in order to complete the reaction. vAcolorless crystalline massis obtained which dissolves in water to give a clear solution. 7

.Emam ple 20 25 parts of the cyclic condensation product from camphorand'glycerine-u-chlorohydrine of the formula which is easily obtainableby a process of analogy (by splitting ofi water in the presence of anauxiliary solvent which makes an azeotropic mixture with water) areheated to -144) C. in an autoclave for 12 hours with 40 parts of amethyl alcoholic dimethylamine solution of '30 per cent. strength. Afterdistilling off the methyl alcohol and the excess dimethyl amine, the

residue. is stirred with concentrated caustic soda is necessary forthemass to-dissolve a-fter boil-r ing. The crystals which formupon-coolin are filtered oil and dried. A white crystal mass isthusobtained. The new. quaternary ammoniumsalt is easily soluble in water,Its aqueous solution, when acidified and heated, soon separates camphorin crystalline form.

Example 21 5 parts of the cyclic .acetal from thujone andglycerine-a-chlorohydrin of the formula oiling point 81-83" 0. [0.07mmJ) whichd's' easily obtainable by a process of analogy lby Its mineralacid while cooling with ice.

"11 splitting -ofi water in the presence ofan auxiliary solvent whichmakes an azeotropic mixture with water) are heated in an autoclave with13 grams of alcoholic dimethyl amine solution of 17.1 per cent.strength, first for five hours to l20-130 C. and then for hours to130-140 C. .After distilling oil the alcohol the residue is dissolved in60 parts of water and the solution is carefully acidifiedwith v dilutehydrochloric After extracting a small quantity of starting material withether, the solution is rendered strongly alkaline with caustic sodasolution, the separated oil taken up in ether and the ethereal solutiondried with potash. After distilling off the ether an oil is ob tainedwhich distills at 94-96 C. (0.05 mm.)'.

1.3 parts of this oil are dissolved'fin 2 parts by volume of absolutealcohol. The'solution is mixed with 0.8 part of methyl iodide while cooling with ice and allowed to stand over night at room temperature. Thesolution solidifies to form a mass of very small crystals which areobtained in pure state afterwashing with ether. They are soluble inwater and when acidified and heated separate thujone. i

What we claim is:

1. Process for the manufacture of an amine of the formula tillation fromthe reaction mixture.

2. An amine of the general formula wherein R is a propyl radicalcontaining two hydroxy groups etherified with a carbonyl com' pound toform a cyclic ether, which amine has a pronounced basic character.

3. The amine" of the formula which amine is a colorless liquid, whichboils at 147-148? C. under 14 mm. pressure, and is soluble incold water.

12 4.- The amine of the formula 0 o v CH3(JH-(Ht \ofifl which amineis acolorless liquid, which boils-at 152-154" C. under 14 mm. pressure, andis soluble in cold water.

5. An amine of the general formula ru m wherein each R1 and each R2 is amember selected from the group consisting of hydrogen and hydrocarbonradicals, which amine has a pronounced basic character. f

6. An amine of the general formula wherein each; R; and each R2 is ahydrocarbon radical, which amine has a pronounced basic character.

7. An amine of the general formula I 1 R1 R;

wherein each R1 and each R2 is an alkyl of low molecular weight, whichamine has a pronounced basic character. H

8. Process for the manufacture of an amine with a pronounced basiccharacter and correspondin tothe-formula. l

.n-N V r y V I I whereinR is a propyl radical containing two hydroxygroups etherified with a carbonylv compound to form a cyclic ether,which process comprises heating a member selected from the groupconsisting oi cyclic acetals of a glycerine-monc- 13 14 chlorhydrin,cyclic acetals of a. glycerine-mono- UNITED STATES PATENTS bromhydrin,cyclic ketals of a giycerine-mono- Number Name Date chlorhydrin andcyclic ketals of a, glycerine- 2091 704 Duncan et 81 Aug 31 1937monobromhydrin with ammonia under pressure 2377105 Reichstein Mas, 1945at a temperature of at least 110 C. 5

RICHARD SALT-MANN. ,4 ,393 Fourneau July 20, 1948 CHARLES GRAENACHER.OTHER R FERENCES REFERENCES CITED lzsgvgzligiizet al., J. Am. Chem. Soc.64, Des. 1291- The following references are of record in the Fourneau etaL, Bull. Soc. Chim. (1945), pages file of this patent: 847 and 848.

5. AN AMINE OF THE GENERAL FORMULA